PMID- 10490030
OWN - NLM
STAT- MEDLINE
DCOM- 19990927
LR  - 20091119
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6749
DP  - 1999 Sep 9
TI  - Crystal structure of nerve growth factor in complex with the ligand-binding
      domain of the TrkA receptor.
PG  - 184-8
AB  - Nerve growth factor (NGF) is involved in a variety of processes involving
      signalling, such as cell differentiation and survival, growth cessation and
      apoptosis of neurons. These events are mediated by NGF as a result of binding to 
      its two cell-surface receptors, TrkA and p75. TrkA is a receptor with tyrosine
      kinase activity that forms a high-affinity binding site for NGF. Of the five
      domains comprising its extracellular portion, the immunoglobulin-like domain
      proximal to the membrane (TrkA-d5 domain) is necessary and sufficient for NGF
      binding. Here we present the crystal structure of human NGF in complex with human
      TrkA-d5 at 2.2 A resolution. The ligand-receptor interface consists of two
      patches of similar size. One patch involves the central beta-sheet that forms the
      core of the homodimeric NGF molecule and the loops at the carboxy-terminal pole
      of TrkA-d5. The second patch comprises the amino-terminal residues of NGF, which 
      adopt a helical conformation upon complex formation, packing against the 'ABED'
      sheet of TrkA-d5. The structure is consistent with results from mutagenesis
      experiments for all neurotrophins, and indicates that the first patch may
      constitute a conserved binding motif for all family members, whereas the second
      patch is specific for the interaction between NGF and TrkA.
FAU - Wiesmann, C
AU  - Wiesmann C
AD  - Department of Protein Engineering, Genentech, Inc., South San Francisco,
      California 94080, USA.
FAU - Ultsch, M H
AU  - Ultsch MH
FAU - Bass, S H
AU  - Bass SH
FAU - de Vos, A M
AU  - de Vos AM
LA  - eng
SI  - PDB/1WWW
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Ligands)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Escherichia coli
MH  - Humans
MH  - Ligands
MH  - Macromolecular Substances
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/*chemistry/metabolism
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins/*chemistry/metabolism
MH  - Receptor Protein-Tyrosine Kinases/*chemistry/metabolism
MH  - Receptor, trkA
MH  - Receptors, Nerve Growth Factor/*chemistry/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
EDAT- 1999/09/18 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/09/18 09:00
PHST- 1999/09/18 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/09/18 09:00 [entrez]
AID - 10.1038/43705 [doi]
PST - ppublish
SO  - Nature. 1999 Sep 9;401(6749):184-8. doi: 10.1038/43705.